tbuckley/cabot-search huggingface dataset:
Speed and Nighttime Usage Restrictions and the Incidence of Shared Electric Scooter Injuries
Authors: Oskari Pakarinen, Arja Kobylin, Veli-Pekka Harjola, Maaret Castrén, Henri Vasara
Journal: JAMA Network Open (2023)

Importance Electric scooter (e-scooter) crashes have become a serious health issue worldwide. The need for effective e-scooter regulations has been established in numerous instances. Objective To investigate the association of restrictions on top speed and nighttime usage on the incidence of e-scooter–related injuries. Design, Setting, and Participants A retrospective comparative cohort study of all patients with an injury related to shared e-scooter riding sustained in Helsinki, Finland. Data were collected from the electric patient database from 3 trauma hospitals representing all public hospitals treating patients with acute trauma in Helsinki. Shared e-scooter injuries from 2 periods were compared: an unrestricted period (January 1 to August 31, 2021) and a restricted period (January 1 to August 31, 2022). Data were analyzed from September 2022 to September 2023. Exposures The restrictions established for shared e-scooters during the restricted period were: (1) the daytime top speed of 20 km/h, as opposed to the previous top speed of 25 km/h, (2) the use of shared e-scooters was prohibited on Friday and Saturday nights between 12 am and 5 am , and (3) the nighttime top speed was decreased to 15 km/h from Sunday to Thursday between 12 am and 5 am , as opposed to 25 km/h. Main outcome The incidence of e-scooter injuries compared with the total trips made by e-scooters. Results There were 528 e-scooter injuries requiring hospital care during the unrestricted period and 318 injuries during the restricted period of similar length. The median (IQR) age of the patients in the study periods was 25 (21-32) and 28 (22-37), respectively; 308 (58%) and 191 (60%) were male, respectively. The incidence of e-scooter injuries was 19 (95% CI, 17-20) for every 100 000 rides during the unrestricted period and 9 (95% CI, 8-10) per 100 000 rides during the restricted period. In the risk analysis, the odds ratio for shared e-scooter injuries was 0.5 (95% CI, 0.4-0.6) for the restricted period when adjusted for hourly temperature, rain amount, wind speed, and visibility. After introducing the restrictions, the number of e-scooter injuries decreased significantly between 11 pm and 5 am. Conclusion and Relevance The number of injuries decreased after implementing restrictions on the top speed and nighttime usage of e-scooters. Similar restrictions in cities with shared e-scooter services should be explored.
Erythroid Differentiation Enhances RNA Mis-Splicing in <i>SF3B1</i>-Mutant Myelodysplastic Syndromes with Ring Sideroblasts
Authors: Pedro L. Moura, Teresa Mortera-Blanco, Isabel J. Hofman, Gabriele Todisco, Warren W. Kretzschmar, Ann-Charlotte Björklund, Maria Creignou, Michael Hagemann-Jensen, Christoph Ziegenhain, David Cabrerizo Granados, Indira Barbosa, Gunilla Walldin, Monika Jansson, Neil Ashley, Adam J. Mead, Vanessa Lundin, Marios Dimitriou, Tetsuichi Yoshizato, Petter S. Woll, Seishi Ogawa, Rickard Sandberg, Sten Eirik W. Jacobsen, Eva Hellström-Lindberg
Journal: Cancer Research (2023)

Myelodysplastic syndromes with ring sideroblasts (MDS-RS) commonly develop from hematopoietic stem cells (HSC) bearing mutations in the splicing factor SF3B1 (SF3B1mt). Direct studies into MDS-RS pathobiology have been limited by a lack of model systems that fully recapitulate erythroid biology and RS development and the inability to isolate viable human RS. Here, we combined successful direct RS isolation from patient samples, high-throughput multiomics analysis of cells encompassing the SF3B1mt stem-erythroid continuum, and functional assays to investigate the impact of SF3B1mt on erythropoiesis and RS accumulation. The isolated RS differentiated, egressed into the blood, escaped traditional nonsense-mediated decay (NMD) mechanisms, and leveraged stress-survival pathways that hinder wild-type hematopoiesis through pathogenic GDF15 overexpression. Importantly, RS constituted a contaminant of magnetically enriched CD34+ cells, skewing bulk transcriptomic data. Mis-splicing in SF3B1mt cells was intensified by erythroid differentiation through accelerated RNA splicing and decreased NMD activity, and SF3B1mt led to truncations in several MDS-implicated genes. Finally, RNA mis-splicing induced an uncoupling of RNA and protein expression, leading to critical abnormalities in proapoptotic p53 pathway genes. Overall, this characterization of erythropoiesis in SF3B1mt RS provides a resource for studying MDS-RS and uncovers insights into the unexpectedly active biology of the "dead-end" RS.
Author Correction: Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial
Authors: Bertrand Routy, John G. Lenehan, Wilson H. Miller, Rahima Jamal, Meriem Messaoudene, Brendan A. Daisley, Cecilia Hes, Kait F. Al, Laura Martinez-Gili, Michal Punčochář, Scott Ernst, Diane Logan, Karl Belanger, Khashayar Esfahani, Corentin Richard, Marina Ninkov, Gianmarco Piccinno, Federica Armanini, Federica Pinto, Mithunah Krishnamoorthy, Rene Figueredo, Pamela Thebault, Panteleimon Takis, Jamie Magrill, LeeAnn Ramsay, Lisa Derosa, Julian R. Marchesi, Seema Nair Parvathy, Arielle Elkrief, Ian R. Watson, Rejean Lapointe, Nicola Segata, S.M. Mansour Haeryfar, Benjamin H. Mullish, Michael S. Silverman, Jeremy P. Burton, Saman Maleki Vareki
Journal: Nature Medicine (2023)
Trends in prevalence of fractures among adults in the United States, 1999–2020: a population-based study
Authors: Bin Xu, Maja R. Radojčić, David B. Anderson, Baoyi Shi, Liang Yao, Yujie Chen, Shiqing Feng, Jae Hyup Lee, Lingxiao Chen
Journal: International Journal of Surgery (2023)

Background: Population data that examine recent national trends in the prevalence of fractures are lacking in the United States (US). Materials and Methods: Analyses were based on 1999–2020 data from National Health and Nutrition Examination Survey (NHANES). Primary outcomes included the prevalence of hip, wrist, and vertebral fractures among adults aged ≥50 years. Changes in the prevalence over time were determined by joinpoint regression analysis. We also described the variation by fracture subtypes, sociodemographic characteristics, and their combination. Results: For adults aged ≥50 years in NHANES 2017-March 2020, we estimated that there was 2.6 million Americans with hip fractures, 14.6 million Americans with wrist fractures, and 5.2 million Americans with vertebral fractures. The prevalence of wrist fractures significantly increased from 8.7% (7.4% to 9.9%) in 1999–2000 to 12.8% (11.6% to 14.1%) in 2017-March 2020 among adults aged ≥50 years ( P for trend = 0.04); significant increases were also observed in fractures that occurred at age &lt;50 years, non-Hispanic White, high family income groups, and several combination subgroups (e.g., fractures occurred at age &lt;50 y among women). The prevalence of vertebral fractures increased from 2.2% (1.7% to 2.8%) in 1999–2000 to 4.6% (3.7% to 5.5%) in 2017-March 2020 among adults aged ≥50 years ( P for trend = 0.02); significant increases were also observed in 50–64 years, women, non-Hispanic White, high family income groups and several combination subgroups (e.g., fractures that occurred at age &lt;50 y among women). We did not observe significant trend changes in the prevalence of hip fractures among adults aged ≥50 years between 1999 and 2020. Conclusion: The estimated prevalence of wrist and vertebral fractures significantly increased among US adults aged ≥50 years from 1999 to 2020, although hip fractures did not significantly change.
The combined HPV16-E2/E6/E7 T cell response in oropharyngeal cancer predicts superior survival
Authors: Saskia J. Santegoets, Anouk Stolk, Marij J.P. Welters, Sjoerd H. van der Burg
Journal: Cell Reports Medicine (2023)

<h2>Summary</h2> Tumor-infiltrating HPV16-E2-specific CD8<sup>+</sup> T cells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4<sup>+</sup> T cells target HPV16 E2 and if HPV16-E2-specific immunity contributes to better clinical outcome is unknown. In a prospective HPV16<sup>+</sup> OPSCC cohort, we regularly detect HPV16-E2-specific CD4<sup>+</sup> and CD8<sup>+</sup> intratumoral T cells, albeit at lower frequencies than the co-infiltrating HPV16-E6/E7-specific T cells. These HPV16-reactive T cells produce multiple cytokines when activated, indicating their polyfunctionality. Importantly, their combined intratumoral presence predicts superior survival, emphasizing the value of HPV16-E2-specific T cells in anti-tumor immunity and suggests its use as a target antigen for immunotherapy.
Prognostic significance of preoperative nutritional status for postoperative acute kidney injury in older patients undergoing major abdominal surgery: a retrospective cohort study
Authors: Rao Sun, Zhiqiang Zhou, Xinhua Li, Qiaoqiao Xu, Biyun Zhou, Honghui Yu, Wanjun Zhang, Qi Sun, Xiang Zhang, Xiaoxiao Luo, Shiyong Li, Ailin Luo
Journal: International Journal of Surgery (2023)

Background: The association between malnutrition and postoperative acute kidney injury (AKI) has not been well studied. In this study, we examined the association between preoperative nutritional status and postoperative AKI in older patients who underwent major abdominal surgery, as well as the predictive value of malnutrition for AKI. Materials and methods: We retrospectively included patients aged 65 or older who underwent major elective abdominal surgery. The nutritional status of the patient was evaluated using 3 objective nutritional indices, such as the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT). AKI was determined using the KDIGO criteria. We performed logistic regression analysis to investigate the association between preoperative nutritional status and postoperative AKI, as well as the predictive value of nutritional scores for postoperative AKI. Results: A total of 2775 patients were included in the study, of which 707 (25.5%), 291 (10.5%), and 517 (18.6%) had moderate to severe malnutrition according to GNRI, PNI, and CONUT calculations. After surgery, 144 (5.2%) patients developed AKI, 86.1% at stage 1, 11.1% at stage 2, and 2.8% at stage 3 as determined by KDIGO criteria. After adjustment for traditional risk factors, worse nutritional scores were associated with a higher AKI risk. In addition to traditional risk factors, these nutritional indices improved the predictive ability of AKI prediction models, as demonstrated by significant improvements in integrated discrimination and net reclassification. Conclusions: Poor preoperative nutritional status, as assessed by GNRI, PNI and CONUT scores, was associated with an increased risk of postoperative AKI. Incorporating these scores into AKI prediction models improved their performance. These findings emphasize the need for screening surgical patients for malnutrition risk. Further research is needed to determine whether preoperative malnutrition assessment and intervention can reduce postoperative AKI incidence.
Microglia in pediatric brain tumors: The missing link to successful immunotherapy
Authors: Aimée du Chatinier, Irene Querol Velilla, Michaël Hananja Meel, Eelco Wieger Hoving, Esther Hulleman, Dennis Serge Metselaar
Journal: Cell Reports Medicine (2023)

Brain tumors are the leading cause of cancer-related mortality in children. Despite the development of immunotherapeutic strategies for adult brain tumors, progress in pediatric neuro-oncology has been hindered by the complex and poorly understood nature of the brain's immune system during early development, a phase that is critical for the onset of many pediatric brain tumors. A defining characteristic of these tumors is the abundance of microglia, the resident immune cells of the central nervous system. In this review, we explore the concept of microglial diversity across brain regions and throughout development and discuss how their maturation stage may contribute to tumor growth in children. We also summarize the current knowledge on the roles of microglia in common pediatric brain tumor entities and provide examples of myeloid-based immunotherapeutic strategies. Our review underscores the importance of microglial plasticity in pediatric brain tumors and its significance for developing effective immunotherapeutic strategies.
Sparsentan — Another Arrow in the Quiver for Treatment of FSGS?
Authors: Julie R. Ingelfinger
Journal: New England Journal of Medicine (2023)

Focal segmental glomerulosclerosis (FSGS), a diagnosis based on glomerular histology,1 carries an ominous prognosis, although its downward slide to end-stage kidney disease is variable. FSGS is a syndrome, and, ultimately, identifying the pathogenesis in each patient might enable the effective individualization of treatment. FSGS is categorized as primary (presumed to be related to permeability factors), secondary, genetic, or unclassified.2 The outcome is poor for most affected persons, irrespective of subtype. Currently, attempts to treat FSGS are nonspecific and often involve glucocorticoids followed by immunosuppressive therapy with calcineurin inhibitors, mTOR inhibitors, anti-CD20 medications such as rituximab, or a combination of these . . .
Predicting response to anti-EGFR antibody, cetuximab, therapy by monitoring receptor internalization and degradation
Authors: Yejin Sung, Seung Taek Hong, Mihue Jang, Eun Sun Kim, Chansoo Kim, Youngmee Jung, Inchan Youn, Ick Chan Kwon, Seung-Woo Cho, Ju Hee Ryu
Journal: Biomaterials (2023)

Anti-epidermal growth factor receptor (EGFR) antibody, cetuximab, therapy has significantly improved the clinical outcomes of patients with colorectal cancer, but the response to cetuximab can vary widely among individuals. We thus need strategies for predicting the response to this therapy. However, the current methods are unsatisfactory in their predictive power. Cetuximab can promote the internalization and degradation of EGFR, and its therapeutic efficacy is significantly correlated with the degree of EGFR degradation. Here, we present a new approach to predict the response to anti-EGFR therapy, cetuximab by evaluating the degree of EGFR internalization and degradation of colorectal cancer cells in vitro and in vivo. Our newly developed fluorogenic cetuximab-conjugated probe (Cetux-probe) was confirmed to undergo EGFR binding, internalization, and lysosomal degradation to yield fluorescence activation; it thus shares the action mechanism by which cetuximab exerts its anti-tumor effects. Cetux-probe-activated fluorescence could be used to gauge EGFR degradation and showed a strong linear correlation with the cytotoxicity of cetuximab in colorectal cancer cells and tumor-bearing mice. The predictive ability of Cetux-probe-activated fluorescence was much higher than those of EGFR expression or KRAS mutation status. The Cetux-probes may become useful tools for predicting the response to cetuximab therapy by assessing EGFR degradation.
The bone transcription factor Osterix controls extracellular matrix- and node of Ranvier-related gene expression in oligodendrocytes
Authors: Benayahu Elbaz, Alaa Darwish, Maia Vardy, Sara Isaac, Haley Margaret Tokars, Yulia Dzhashiashvili, Kirill Korshunov, Murali Prakriya, Amir Eden, Brian Popko
Journal: Neuron (2023)
Dissecting the intricacies of human antibody responses to SARS-CoV-1 and SARS-CoV-2 infection
Authors: Ruoke Wang, Yang Han, Rui Zhang, Jiayi Zhu, Xuanyu Nan, Yaping Liu, Ziqing Yang, Bini Zhou, Jinfang Yu, Zichun Lin, Jinqian Li, Peng Chen, Yangjunqi Wang, Yujie Li, Dongsheng Liu, Xuanling Shi, Xinquan Wang, Qi Zhang, Yuhe R. Yang, Taisheng Li, Linqi Zhang
Journal: Immunity (2023)
Zibotentan in combination with dapagliflozin compared with dapagliflozin in patients with chronic kidney disease (ZENITH-CKD): a multicentre, randomised, active-controlled, phase 2b, clinical trial
Authors: Hiddo J L Heerspink, Arihiro Kiyosue, David C Wheeler, Min Lin, Emma Wijkmark, Glenn Carlson, Anne-Kristina Mercier, Magnus Åstrand, Sebastian Ueckert, Peter J Greasley, Phil Ambery
Journal: The Lancet (2023)
Identification of genetic profile and biomarkers involved in acute respiratory distress syndrome
Authors: Shurui Cao, Huiqin Li, Junyi Xin, Zhenghao Jin, Zhengyu Zhang, Jiawei Li, Yukun Zhu, Li Su, Peipei Huang, Lei Jiang, Mulong Du, David C. Christiani
Journal: Intensive Care Medicine (2023)
Assessment of angle closure disease in the age of artificial intelligence: A review
Authors: Zhi Da Soh, Mingrui Tan, Monisha Esther Nongpiur, Benjamin Yixing Xu, David Friedman, Xiulan Zhang, Christopher Leung, Yong Liu, Victor Koh, Tin Aung, Ching-Yu Cheng
Journal: Progress in Retinal and Eye Research (2023)
The ubiquitin-like modifier FAT10 is induced in MASLD and impairs the lipid-regulatory activity of PPARα
Authors: Ludivine Clavreul, Lucie Bernard, Alexia K. Cotte, Nathalie Hennuyer, Cyril Bourouh, Claire Devos, Audrey Helleboid, Joel T. Haas, An Verrijken, Céline Gheeraert, Bruno Derudas, Loïc Guille, Julie Chevalier, Jérôme Eeckhoute, Emmanuelle Vallez, Emilie Dorchies, Luc Van Gaal, Guillaume Lassailly, Sven Francque, Bart Staels, Réjane Paumelle
Journal: Metabolism (2023)
Combating KRASG12C Inhibitor Resistance
Journal: Cancer Discovery (2023)

To boost KRASG12C inhibitor efficacy and counter cancer cells' ability to mount resistance, combination strategies are being utilized. Findings from the phase III CodeBreaK 300 trial indicate that adding the EGFR inhibitor panitumumab to sotorasib bests standard care for chemorefractory KRASG12C colorectal cancer. Joint SHP2 blockade is another approach that shows signs of activity in reversing acquired KRASG12C inhibitor resistance, according to preliminary phase I data.
Annotation of cell types (ACT): a convenient web server for cell type annotation
Authors: Fei Quan, Xin Liang, Mingjiang Cheng, Huan Yang, Kun Liu, Shengyuan He, Shangqin Sun, Menglan Deng, Yanzhen He, Wei Liu, Shuai Wang, Shuxiang Zhao, Lantian Deng, Xiaobo Hou, Xinxin Zhang, Yun Xiao
Journal: Genome Medicine (2023)

The advancement of single-cell sequencing has progressed our ability to solve biological questions. Cell type annotation is of vital importance to this process, allowing for the analysis and interpretation of enormous single-cell datasets. At present, however, manual cell annotation which is the predominant approach remains limited by both speed and the requirement of expert knowledge.To address these challenges, we constructed a hierarchically organized marker map through manually curating over 26,000 cell marker entries from about 7000 publications. We then developed WISE, a weighted and integrated gene set enrichment method, to integrate the prevalence of canonical markers and ordered differentially expressed genes of specific cell types in the marker map. Benchmarking analysis suggested that our method outperformed state-of-the-art methods.By integrating the marker map and WISE, we developed a user-friendly and convenient web server, ACT ( http://xteam.xbio.top/ACT/ or http://biocc.hrbmu.edu.cn/ACT/ ), which only takes a simple list of upregulated genes as input and provides interactive hierarchy maps, together with well-designed charts and statistical information, to accelerate the assignment of cell identities and made the results comparable to expert manual annotation. Besides, a pan-tissue marker map was constructed to assist in cell assignments in less-studied tissues. Applying ACT to three case studies showed that all cell clusters were quickly and accurately annotated, and multi-level and more refined cell types were identified.We developed a knowledge-based resource and a corresponding method, together with an intuitive graphical web interface, for cell type annotation. We believe that ACT, emerging as a powerful tool for cell type annotation, would be widely used in single-cell research and considerably accelerate the process of cell type identification.
A 3D In Vitro Cortical Tissue Model Based on Dense Collagen to Study the Effects of Gamma Radiation on Neuronal Function
Authors: Neal M. Lojek, Victoria A. Williams, Andrew M. Rogers, Erno Sajo, Bryan J. Black, Chiara E. Ghezzi
Journal: Advanced Healthcare Materials (2023)

Studies on gamma radiation-induced injury have long been focused on hematopoietic, gastrointestinal, and cardiovascular systems, yet little is known about the effects of gamma radiation on the function of human cortical tissue. The challenge in studying radiation-induced cortical injury is, in part, due to a lack of human tissue models and physiologically relevant readouts. Here, a physiologically relevant 3D collagen-based cortical tissue model (CTM) is developed for studying the functional response of human iPSC-derived neurons and astrocytes to a sub-lethal radiation exposure (5 Gy). Cytotoxicity, DNA damage, morphology, and extracellular electrophysiology are quantified. It is reported that 5 Gy exposure significantly increases cytotoxicity, DNA damage, and astrocyte reactivity while significantly decreasing neurite length and neuronal network activity. Additionally, it is found that clinically deployed radioprotectant amifostine ameliorates the DNA damage, cytotoxicity, and astrocyte reactivity. The CTM provides a critical experimental platform to understand cell-level mechanisms by which gamma radiation (GR) affects human cortical tissue and to screen prospective radioprotectant compounds.
MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC
Authors: Naoki Haratake, Hiroki Ozawa, Yoshihiro Morimoto, Nami Yamashita, Tatsuaki Daimon, Atrayee Bhattacharya, Keyi Wang, Ayako Nakashoji, Hideko Isozaki, Mototsugu Shimokawa, Chie Kikutake, Mikita Suyama, Asato Hashinokuchi, Kazuki Takada, Tomoyoshi Takenaka, Tomoharu Yoshizumi, Tetsuya Mitsudomi, Aaron N. Hata, Donald Kufe
Journal: Journal of Thoracic Oncology (2023)

IntroductionOsimertinib is an irreversible EGFR tyrosine kinase inhibitor approved for the first-line treatment of patients with metastatic NSCLC harboring EGFR exon 19 deletions or L858R mutations. Patients treated with osimertinib invariably develop acquired resistance by mechanisms involving additional EGFR mutations, MET amplification, and other pathways. There is no known involvement of the oncogenic MUC1-C protein in acquired osimertinib resistance.MethodsH1975/EGFR (L858R/T790M) and patient-derived NSCLC cells with acquired osimertinib resistance were investigated for MUC1-C dependence in studies of EGFR pathway activation, clonogenicity, and self-renewal capacity.ResultsWe reveal that MUC1-C is up-regulated in H1975 osimertinib drug-tolerant persister cells and is necessary for activation of the EGFR pathway. H1975 cells selected for stable osimertinib resistance (H1975-OR) and MGH700-2D cells isolated from a patient with acquired osimertinib resistance are found to be dependent on MUC1-C for induction of (1) phospho (p)-EGFR, p-ERK, and p-AKT, (2) EMT, and (3) the resistant phenotype. We report that MUC1-C is also required for p-EGFR, p-ERK, and p-AKT activation and self-renewal capacity in acquired osimertinib-resistant (1) MET-amplified MGH170-1D #2 cells and (2) MGH121 Res#2/EGFR (T790M/C797S) cells. Importantly, targeting MUC1-C in these diverse models reverses osimertinib resistance. In support of these results, high MUC1 mRNA and MUC1-C protein expression is associated with a poor prognosis for patients with EGFR-mutant NSCLCs.ConclusionsOur findings reveal that MUC1-C is a common effector of osimertinib resistance and is a potential target for the treatment of osimertinib-resistant NSCLCs.
Buprenorphine Versus Diclofenac for Pain Relief in Acute Pancreatitis: A Double-Blinded Randomized Controlled Trial
Authors: Mayank Saini, Jayanta Samanta, Antriksh Kumar, Arup Choudhury, Jahnvi Dhar, Anudeep Jafra, Rajeev Chauhan, Gaurav Muktesh, Pankaj Gupta, Vikas Gupta, Thakur Deen Yadav, Rakesh Kochhar, Gabriele Capurso, Enrique De-Madaria, Antonio Facciorusso
Journal: Clinical Gastroenterology and Hepatology (2023)